Blister process in pharmaceutical industry
Blister process in the pharmaceutical industry
The blister was first used in the 50´as a primary packing in the pharmaceutical industry.
A design developed by Shering Germany for a tablet to be used by women was the beginning of
the blister.
With the advances in technology, the packing in blisters was applied to the many pharmaceutical
products that we know today.
In this course we will see the concept of the process, some common problems and some useful
tips.
Medicine packing requirements
Article 21, Part 211 del Code of Federal Regulations, Food and Drugs, states:
“the packing and closure of medicines can not be reactive, adictive, or absorved
to garantee the safety, identity, eficiency, quality and purity of the drug beyond
the oficial or stablished requirements. The sealing system should offer the
adecuate protection against adverse external conditions expected during storage
and use that could harm or contaminate the product”.
The blister as a primary packing
Phisical and Chemical barrier that protects the product against external
agents.
Advantages in the use of blister:
1) Product integrity
2) Protection of product
3) Tamper proof
4) Low possibility of accidental overdose
5) Compliance with pacient favoring guidelines
6) Generation of identifiable single doses
Tipical process
1.
2.
3.
4.
5.
6.
Forming
Product loading
Sealing
Coding
Perforation
Cut
Forming materials
.- Thermoforming:
Single layer:
Multilayer:
PVC
PVC + PVdC
PVC + PCTFE (Aclar)
Material selection criteria.
Coldforming:
Multilayer:
Cold Forming Foil
Product been packed.
Enviroment.
Marketing and sales.
Costs.
Available equipment
.
Heat forming
Termo formable materials: Thermo plastic polimers PVC / PVDC / ACLAR®
Definition: union of hundreds of thousands of small molecules
“monómers” that form huge chains.
Amorfus structure
Cristalline structure
PVC (PolyVinyl Chloride)
.- It is the most widely used due to its cost/ protection ratio.
.- Its the material with the least protection.
.- It is used as the base for the rest of muti layers including Alu-Alu.
.- The blistering process is the most standard.
PVC + PVdC (PolyVinyl DiChloride )
.- It is a two-layer material with PVC as a base, with al ayer of PVdC.
.- Depending on the thickness of the PVdC (from 60 g/m2) low to medium
protection is obtained.
.- Special care in design and construction of tooling. Heating plates to be
lined with non-stick surface
.- Toxic and corrosive gases (HCl) are produced during heating.
.- As two materials are involved, different temperatures are to be chosen in
each side of the heating plates.
.- Forming plug-assist is recomended.
PVC + PCTFE (Policlorotrifluoretileno – Aclar)
.- It is a two layer material with PVC as base and an adittional layer of Aclar.
.- Depending on the thickness of the Aclar layer (from 15 microns) medium to
high protection is achived.
.- Special care in design and construction of tooling. Heating plates to be lined
with non-stick surface.
.- As two materials are involved, different temperatures are to be chosen in
each side of the heating plates .
.- Forming plug-assist is recomended.
Thermoforming
Thermoplastics
The temperature is raised to anable forming
Contact
Heating plates
Heating coils
Tunnel
Thermoforming
2
1
T
E
Molecular movility
3
T
Transitory deformation
4
E
Molecular movility
Permanent deformation
Thermoforming
Positive air pressure
Thermoforming
Plug-assisted forming.
Cold forming foil.
.- It is a multi-layer material whose main component is alumminum.
.- Gives the best protection.
.- Tle film is composed of PVC (inside layer of the blister), OPA and
adhesives.
.- the PVC and OPA give better forming and structural characteristics to
alumminum.
Cold forming
Cold forming
Fisures in Alu-Alu blisters
Fisure causes:
• Excesive streching.
• Tooling defects.
• Wrong set up.
• Material problems.
( 25 µm fisure)
Comparison between cold forming Vs. thermoforming.
Size differences in thermoplastic vs. alu cold forming
Comparing cold forming Vs. Thermoforming.
.- Less efficient process.
.- Bigger alveoluses → Bigger blisters → Less blister per cycle.
→ less tablets per blister.
.- More complex forming means less speed.
.- Need to have microfisures detection hardware
.- More complex loading
→ Manual loading is slow and ineficient.
→ More expensive mechanical loading devises.
.- No visual inspection can be done once the blister is sealed.
.- Blister fragility.
Blisters
Product feedidng
To be considered :
1.
Batch size
2.
Type of product / characteristics
3.
Blister design/ geometry / graphics
4.
Type of barrier (PVC, Aclar®, Alu Alu)
5.
Powder / aspiration
Alternatives:
1.
Manual feeding
2.
Semi-automatic feeder
3.
Universal automatic feeder
4.
Dedicated automatic feeder
• Manual
Vacuum
manifold
• Semi-automatic feeder
Vacuum
• Automatic Universal Feeder
Sealing
The base and sealing material are sealed by pressure and temperature
Lidding material (Alumminum).
Thermosealing laquers
The functional characteristics of the the lacquer is to act as a thermosealing
agent between the PVC or PVDC and the lidding material.
It is a critical component as it has to assure:
- Intimate sealing between PVC and alumminum
(hermeticity)
- Sealing at relatibly low temperatures
(inks, barnishes and product degradation)
- Dimensional stability
(deformation)
- Dstability in time of the union
(aging)
- Inocuity
(Tablet contamination from solvents or decomposition of polimers into free
monomers)
Sealing
Thermosealing
lacquer
Forming material (PVC o PVDC)
P, T, t
Coding
Perforation
One way
Two way
Die-Cutting
Simple efect
Cut
Doble efect
(Saves material)
Main accesories and optionals
•
Plug-Assisted forming system.
•
Cold forming system.
•
Pin-Hole detector.
•
Feeders.
•
Print mark registrarion - Fotocentering
device (centered printing).
•
In-line printer.
• Filling Inspection Systems.
•
Blister positioner
•
Exit conveyor belt.
•
Rejection sistem
•
Others
– Bar code reader.
– Assisted sealing.
Photo centering – Mark reader and step corrector
The blister uses lidding material with
centerd printing.
Ej:
Monodose
Medical samples.
Etc.
Photo centering – Mark reader and step corrector
start: Light ray inside the mark.
HAZ DE LUZ
1.- Step is longer than the nominal for the
lidding material.
SENSOR DE CONTRASTE
TACO
SISTEMA DE AVANCE CON
CORRECTOR
Mark moves downward.
2.- moves forward with the same step: the
light is outside the mark.
Sensor sends a signal: the corrector is
activated.
3.- The step corrector shortens the advance
distance.
The markreturns to the original position.
La impresión constantemente se desplaza respecto del
corte, dentro de valores determinados.
In-line printer.
.-Lidding material is blank. It is printed
directly beforo sealing.
.- More efficient stock managment.
Printer types.
.- Flexographic.
.- Thermal transfer.
Load inspection systems.
Vision inspection are the most widely
used.
Capable of verifing presence, position,
colour and broken tablets.
Must be used along with the blister
positioner and some rejection system.
INSPECTION
FEEDER
DIE-CUTTING
BLISTER
POSITIONER
REJECTION
SEALING
Blister positioner
Prevents the blister from being retained in the die-cutting tool
If a vaccum- actuated suction cup system is included, it places them on the exit belt
helping reject and transfer
Discard.
•
Complete step
– Discards all the blister in 1 step.
•
Individual
– Discards only the faulty blister.
•
Pick and Place
– The concept is not to reject the bad ones but to take the good ones at the end of
the operation.
•
Discard control.
– Sensors verify that discard is done.
Blister design